Effects of Different Doses of Nucleocapsid Protein from Hantaan Virus A9 Strain on Regulation of Interferon Signaling.

Hantaan virus A9 strain (HTNV A9) is an etiologic agent of hemorrhagic fever with renal syndrome in China. The virulence of the pathogenic hantaviruses is determined by their ability to alter key signaling pathways of early interferon (IFN) induction within cells. The potential role of HTNV A9 structural proteins, such as nucleocapsid (N) and envelope glycoproteins (Gn and Gc), in regulating human's innate antiviral immune response has not yet been clarified. In this study, we investigated the effect of HTNV A9 N protein on the regulation of the IFN pathway. We found that A9 N protein can influence the host innate immune response by regulating the activation of IFNβ. The A9 N protein stimulates IFN response in low doses, whereas significantly inhibits IFNβ production at high doses. Furthermore, A9 N protein constitutively inhibits nuclear factor kappa B activation. A high dose of A9 N protein could inhibit either Poly IC-induced IFNβ or vesicular stomatitis virus-induced IFNβ and interferon-stimulated gene production. Our results indicate that HTNV A9 N protein helps virus establish successful infection by downregulating the IFN response and shed new light to the understanding of the interaction between the host innate immunity and virus during Hantaan virus infection.